PTH induces bone loss via microbial-dependent expansion of intestinal TNF+ T cells and Th17 cells

Mingcan Yu, Abdul Malik Tyagi, Jau-Yi Li, Jonathan Adams, Timothy L. Denning, M. Neale Weitzmann, Rheinallt M. Jones and Roberto Pacifici ()
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Mingcan Yu: Emory University
Abdul Malik Tyagi: Emory University
Jau-Yi Li: Emory University
Jonathan Adams: Emory University
Timothy L. Denning: Georgia State University
M. Neale Weitzmann: Emory University
Rheinallt M. Jones: Emory University
Roberto Pacifici: Emory University

Nature Communications, 2020, vol. 11, issue 1, 1-17

Abstract: Abstract Bone loss is a frequent but not universal complication of hyperparathyroidism. Using antibiotic-treated or germ-free mice, we show that parathyroid hormone (PTH) only caused bone loss in mice whose microbiota was enriched by the Th17 cell-inducing taxa segmented filamentous bacteria (SFB). SFB+ microbiota enabled PTH to expand intestinal TNF+ T and Th17 cells and increase their S1P-receptor-1 mediated egress from the intestine and recruitment to the bone marrow (BM) that causes bone loss. CXCR3-mediated TNF+ T cell homing to the BM upregulated the Th17 chemoattractant CCL20, which recruited Th17 cells to the BM. This study reveals mechanisms for microbiota-mediated gut–bone crosstalk in mice models of hyperparathyroidism that may help predict its clinical course. Targeting the gut microbiota or T cell migration may represent therapeutic strategies for hyperparathyroidism.

Date: 2020
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DOI: 10.1038/s41467-019-14148-4

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